Severe valvular and aortic arch calcification in a patient with gaucher's variant homozygous for D409h mutation

Abstract

Gaucher's disease is an autosomal recessive inherited defect of the lysosomal enzyme glucocerebrosidase which leads to glucocerebroside accumulation in the reticuloendothelial system. The most common mutations are N370S and 84 gg which lead to bone fractures, organomegaly and cytopenias. We present a case of a 17 year old Palestinian patient who presented in 7/97 with severe aortic and mitral valvular calcification, as well as calcification of the ascending aorta, the aortic arch and the ostia of his coronary arteries. The patient was confirmed to be homozygous for the D409H mutation of the glucocerebrosidase gene. The patient's enzyme assay for glucocerebrosidase activity was 5 nm/hr/mg protein (normal 13–22 nm/hr/mg). The patient presented with symptoms of dyspnea and chest pain. He had a history of documented aortic valve calcification that was diagnosed in 1991 by echocardiogram after two of his older brothers died of congestive heart failure and severe valvular calcification. Cardiac catheterization on 7/30/99 showed a severely calcified aorta with almost no motion of the aortic valve leaflets and severe calcification of the mitral valve and the mitral valvular apparatus. On 8/5/97 patient underwent extensive cardiac surgery with aortic and mitral valve replacements and intraoperative findings confirmed calcification of the entire aortic root. Electron microscopy of the valves confirmed the presence of Gaucher's bodies. Enzyme therapy with imiglucerase was initiated in the perioperative period and patient was in stable condition at last follow-up in 12/99. Previous reports of patients with the D409H mutation note this unusual phenotype with severe calcification of the aortic and mitral valves.